Cytokine-induced selective increase of high-molecular-weight bFGF isoforms and their subcellular kinetics in cultured rat hippocampal astrocytes

Abstract

Cytokines such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and epidermal growth factor (EGF) are probable factors responsible for up-regulation of basic fibroblast growth factor (bFGF) expression in reactive astrocytes following brain damage, however the effect of these cytokines on the expression of each bFGF-isoform has not been elucidated. Western blot analysis revealed the expression of 18, 22 and 24-kD bFGF isoforms in cultured rat hippocampal astrocytes, and the expression of high molecular weight (HMW)-isoforms (22 and 24-kD isoforms) but not of 18-kD isoform was selectively increased by cytokines. Immunofluorescent analysis demonstrated that bFGF content in the cytoplasm of astrocytes is initially increased by cytokines followed by nuclear targeting and localization in agreement with the previous evidence that HMW-isoforms possess a nuclear targeting signal. The present results suggest the important role of HMW-bFGF isoforms in the response of nervous tissue to injury.

Adult Neurogenesis: From Precursors to Network and Physiology

“…Astrocytes, which play an important role as sensors of changes in their extracellular microenvironment, could regulate neurogenesis by secreting local signals (514). These signals, unknown so far, may be ionic fluxes, neurosteroids, cytokines, growth factors, and glutamate metabolites (48,243,245,296,486,516,579,595). The observation that some proliferating cells in the DG express a receptor for S100␤, a small acidic calcium binding neurotrophic protein released by astrocytes, reinforces the putative contribution of glial cells in the regulation of adult neurogenesis (339).…”

Epidermal growth factor differentially regulates low density lipoprotein receptor-related protein gene expression in neoplastic and fetal human astrocytes

“…Activation of EGFR signaling pathway(s) and EGFR amplification are important biological determinants of malignant progression in astrocytic tumors (Lund-Johansen et al, 1990;Torp et al, 1991;Lang et al, 1994;Chicoine et al, 1995). In neoplastic and reactive astrocytes, EGF also synergizes the activity of other growth factors, including insulin-like growth factor-1 (IGF-1) (Chernausek, 1993;Faber-Elman et al, 1996), and up-regulates basic fibroblast growth factor (bFGF) expression (Kamiguchi et al, 1996). In the setting of subacute and chronic reactive astocytosis, EGF may also mediate a number of neuronal-glial interactions via direct and indirect mechanisms (Junier et al, 1994).…”

Nuclear Activities of Basic Fibroblast Growth Factor: Potentiation of Low-Serum Growth Mediated by Natural or Chimeric Nuclear Localization Signals

“…Although various cells produce FGF-2, only a small amount of data concerning the differential expression and regulation of FGF-2 isoforms has been reported; however, it has been demonstrated that the relative amounts of the individual forms of FGF-2 vary among cell types and tissues during development and in adulthood (Giordano et al, 1992;Liu et al, 1993;Dono and Zeller, 1994;Coffin et al, 1995;Riese et al, 1995;Vagner et al, 1996) Moreover, a recent report shows a cytokine-specific induction of HMW FGF-2 in rat astrocytes (Kamiguchi et al, 1996) and a direct correlation between HMW isoform expression and stress conditions such as heat shock and oxidative stress in normal cells (Vagner et al, 1996). Different FGF-2 isoforms have been overexpressed in both transgenic mice (Davis et al, 1997) and various normal and transformed cell lines (Pasumarthi et al, 1994(Pasumarthi et al, , 1996Joy et al, 1997;Dono et al, 1998;Grothe et al,1998).…”

“…Moreover, the 22-and 22.5-kDa forms of human HMW FGF-2 expressed in NIH 3T3 cells contain five dimethylarginines located in their respective amino-terminal extensions, and the 24-kDa form contains up to eight dimethylarginines (Klein, unpublished data). Pintucci et al (1996) showed that the translocation of newly synthesized HMW FGF-2 into the nucleus is accompanied by posttranslational methylation and that a methyltransferase inhibitor markedly reduces the nuclear accumulation of endogenous HMW FGF-2.Although various cells produce FGF-2, only a small amount of data concerning the differential expression and regulation of FGF-2 isoforms has been reported; however, it has been demonstrated that the relative amounts of the individual forms of FGF-2 vary among cell types and tissues during development and in adulthood (Giordano et al, 1992;Liu et al, 1993;Dono and Zeller, 1994;Coffin et al, 1995;Riese et al, 1995;Vagner et al, 1996) Moreover, a recent report shows a cytokine-specific induction of HMW FGF-2 in rat astrocytes (Kamiguchi et al, 1996) and a direct correlation between HMW isoform expression and stress conditions such as heat shock and oxidative stress in normal cells (Vagner et al, 1996). M. Arese et al…”